What is the prognosis and treatment for low-grade endometrial stromal sarcoma?

Low-Grade Endometrial Stromal Sarcoma: Prognosis and Treatment

Low-grade endometrial stromal sarcoma (LGESS) has an excellent prognosis with overall survival rates that often cannot be reached in long-term studies, with 88% of patients still alive at 80 months follow-up. 1

Prognostic Factors

LGESS demonstrates a significantly more favorable prognosis compared to other uterine sarcomas:

• Histopathology: LGESS is characterized by small cells with low-grade cytology resembling proliferative endometrial stroma with low mitotic activity (usually <5 mitotic figures per 10 HPF) 1
• Disease presentation: LGESS patients are significantly more likely to present with uterine/cervix-confined disease (68% vs 39% in high-grade ESS) 1
• Survival rates:
  • Median overall survival for LGESS is not reached in most studies, compared to 53 months for high-grade ESS and 16.5-21 months for other uterine sarcomas 1
  • Five-year survival rate is approximately 93% 2

Favorable prognostic indicators:

• Absence of myometrial invasion 2
• Low mitotic count (≤5/HPF) 2
• Disease limited to the uterus 3

Treatment Approach

Surgical Management

1. Primary treatment: Total abdominal hysterectomy with bilateral salpingo-oophorectomy (TAH-BSO) is the standard surgical approach 1

   • Routine lymphadenectomy is not indicated as lymph node involvement is less than 5% 1
   • Retention of ovaries may be considered in pre-menopausal women, though bilateral oophorectomy is generally indicated 1

2. For recurrent disease:

   • Surgical cytoreduction should be considered even in cases with extensive disease 4
   • Complete cytoreduction is associated with improved outcomes 4

Hormonal Therapy

For recurrent or metastatic disease:

• First-line: Estrogen deprivation therapy with aromatase inhibitors or progestogens 1
• Contraindicated: Tamoxifen (not recommended due to potential pro-estrogenic effects) 1
• Post-operative considerations: Hormone replacement therapy is contraindicated 1

Adjuvant Therapy

• Radiotherapy: Not routinely indicated in FIGO stage I and II disease as it has not been shown to improve survival 1
• Hormonal therapy: No routine role for adjuvant hormonal treatment due to lack of supporting evidence 1
• Chemotherapy: Reserved for cases where hormonal therapy fails 1

Recurrence Patterns

• Recurrence risk is significant, ranging from 1 in 3 to 1 in 2 patients 4
• Recurrences often occur late, even beyond 5 years after initial treatment 5
• Local pelvic recurrence is the most common pattern 3
• Median time to recurrence is approximately 36 months (range 4-108 months) 3

Surveillance Recommendations

Long-term surveillance is crucial due to the tendency for late recurrence:

• Regular follow-up examinations for at least 5-10 years
• Consider extended hormonal therapy beyond 5 years to prevent late recurrence 5

Special Considerations

• Vascular invasion: LGESS can invade blood vessels, occasionally presenting with intravascular extension 4
• Fertility preservation: Has been described in selected cases but carries risk of recurrence 5
• Molecular features: Homozygous deletion of CDKN2A may be associated with poor prognosis and resistance to hormonal therapy 6

Treatment Algorithm for Recurrent Disease

1. First-line: Estrogen deprivation therapy (aromatase inhibitors or progestogens)
2. If hormone therapy fails: Consider chemotherapy (doxorubicin-based regimens)
3. For isolated or resectable recurrences: Surgical cytoreduction
4. For selected cases: Consider targeted therapies like pazopanib after failure of standard approaches

Given the indolent nature of LGESS, the excellent long-term prognosis, and the potential for late recurrence, lifelong surveillance and consideration of extended hormonal therapy are warranted.